Statistical Methods for Estimating LTD10 from
TD50 and Its Lower Confidence Limit

LTD10 is the lower 95% confidence
limit on the dose to induce tumors in 10% of animals.
LTD10 values are estimated from the CPDB using the
TD50 and 99% lower confidence limit as follows:

Both the TD50 and the
two-sided 99% confidence limits (LoConf, UpConf) are reported in
the CPDB from fitting the one-hit
model to experimental dose-response data using maximum likelihood
methods. The one-hit model was selected because it is the most
conservative of the multistage models. When both the
TD50 and the two-sided 99% confidence limits are
available, it is shown in Gold et al. (2003) for the one-hit
model that the lower 95% confidence limit for the TD10,
i.e., LTD10 is:

LTD10 = [(TD50)0.36
× (LoConf)0.64] / 6.6

Since the one-hit model is the most conservative form of the family
of multistage models of carcinogenesis, the above estimate of the
LTD10 provides at least 95% confidence that the true
value of the TD10 is above this lower confidence limit
for this family of models.

This method gave similar estimates to the LTD10
obtained by fitting the multistage model to the tumor incidence
data for both linear and curved dose responses with high or low
tumor rates in the controls and tight or wide confidence limits for
the TD50 (Gold et al., 2003). Thus, relatively
precise estimates of the LTD10 can be readily calculated
from the TD50 and LoConf from the CPDB.

LTD10 values are reported in
an Excel spreadsheet in each species
for all chemicals in the CPDB with a positive evaluation of
carcinogenicity by the author of at least one experiment.